Exploratory studies revealed that AZT exposure down-regulated the microRNA hsa-miR-770-5p in the mammary epithelial cell line MCF10A. We therefore chose to study the hsa-miR-770-5p target gene Stathmin1 (STMN1), because the concomitant upregulation of this gene would cause microtubule erosion and mitotic spindle destabilization. Our previous studies showed that, after exposure to AZT, about 25% of normal human mammary epithelial cells (NHMECs) lacked the ability to polymerize microtubules. We performed reverse transfections to introduce overexpression of hsa-miR-770-5p (defined as mimic) and inhibition of hsa-miR-770 (defined as inhibitor) in MCF10A cells. We found that STMN1 RNA expression increased when hsa-miR-770-5p levels were very low, and confirmed this finding by Western blot. Therefore, down-regulation of hsa-miR-770-5p caused an increase in STMN1 expression, suggesting that AZT-induced genomic instability may occur through dysregulation of STMN1 and tubulin erosion. The manuscript is in progress. Monkey studies Truvada, the combination of a protease inhibitor tenofovir, and an NRTI emtricitabine, is used increasingly in human pregnancy and also for pre-exposure prophylaxis in non-HIV-1-infected adults. We currently have 3-4 monkeys taken at birth after in utero exposure to truvada, and are analyzing these for genotoxicity and mitochondrial toxicity. We are interested in examining agents that might protect heart and brain from toxicities induced by NRTI therapy. Previously we showed that Tempol and Tempol-H protect mitochondria of cultured cardiomyocytes from NRTI-induced damage. Currently we are analyzing at birth offspring of patas dams given no drugs, AZT/3TC alone, AZT/3TC/Tempol or Tempol alone. Analysis of heart tissue EMs has demonstrated that infants given AZT/3TC/Tempol are protected from mitochondrial damage seen with AZT/3TC. Examination of brain and bone marrow cells is in progress.